Hospital Practice

ISSN: 2154-8331 (Print) 2377-1003 (Online) Journal homepage: http://www.tandfonline.com/loi/ihop20

Ceftaroline fosamil for the treatment of hospitalacquired pneumonia and ventilator-associated pneumonia Keith S. Kaye, George Udeani, Phillip Cole & Hillel David Friedland To cite this article: Keith S. Kaye, George Udeani, Phillip Cole & Hillel David Friedland (2015) Ceftaroline fosamil for the treatment of hospital-acquired pneumonia and ventilatorassociated pneumonia, Hospital Practice, 43:3, 144-149 To link to this article: http://dx.doi.org/10.1080/21548331.2015.1037228

Published online: 08 May 2015.

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Date: 10 September 2015, At: 18:37

http://informahealthcare.com/hop ISSN: 2154-8331 (print) Hosp Pract, 2015; 43(3): 144–149 DOI: 10.1080/21548331.2015.1037228

CLINICAL FOCUS: INFECTIOUS DISEASES ORIGINAL RESEARCH

Ceftaroline fosamil for the treatment of hospital-acquired pneumonia and ventilator-associated pneumonia Keith S. Kaye1, George Udeani2, Phillip Cole3 and Hillel David Friedland3 Detroit Medical Center and Wayne State University, University Health Center, Detroit, MI, USA, 2Corpus Christi Medical Center, Doctors Regional Hospital, Department of Pharmacy, Corpus Christi, TX, USA, and 3Cerexa, Inc., Oakland, CA, USA

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1

Abstract

Keywords

Objectives: Ceftaroline fosamil is a novel cephalosporin with bactericidal activity against common pathogens associated with hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP). Ceftaroline is inactive against extended-spectrum b-lactamase-producing or AmpCoverexpressing Enterobacteriaceae and has limited activity against Pseudomonas aeruginosa. CAPTURE is a multicenter, retrospective study designed to collect information on contemporary clinical use of ceftaroline fosamil in the USA. Data on off-label use of ceftaroline fosamil for the treatment of patients with HAP/VAP between September 2013 and March 2014 are presented. Methods: Data were collected at participating study centers by randomized selection and review of patients’ charts, and included patients’ demographics, disease characteristics, pathogens isolated, antibiotic treatment and clinical outcomes. Patients receiving at least four consecutive doses of ceftaroline fosamil, with data available for determination of clinical cure, comprised the evaluable population. Clinical success was defined as either clinical cure with no further need for antibiotics treatment, or clinical improvement with a switch to another antibiotic. Results: A total of 40 patients were evaluated: 27 with HAP and 13 with VAP. Demographics for patients with HAP and VAP were similar (59% male, mean age of 63 years and 54% male, mean age of 58 years, respectively). The clinical success rates were 75% overall, 82% in patients with HAP and 62% in patients with VAP. Clinical success rates for patients with methicillin-resistant Staphylococcus aureus (MRSA) isolated were 58% in patients with HAP and 57% in patients with VAP. Ceftaroline fosamil was used as a second-line therapy in majority of patients (85%) with clinical success rates of 79% similar to the published literature. Conclusion: The CAPTURE study data support further evaluation of ceftaroline fosamil as an effective treatment option for HAP and VAP when a ceftaroline susceptible etiologic pathogen is identified, including MRSA, or as a concurrent therapy when resistant Gram-negative pathogens are suspected.

Hospital-acquired pneumonia, ventilatorassociated pneumonia, ceftaroline fosamil, CAPTURE

Introduction Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) are significant causes of morbidity, mortality, and healthcare resource utilization. HAP is a pulmonary infection caused by infectious agents not present or not incubating at the time of the patient’s hospital admission, i.e. an infection that develops > 48 h after hospital admission. VAP is a subset of HAP arising in mechanically ventilated patients > 48–72 h after endotracheal intubation [1]. Almost a third of HAP are acquired in the intensive care unit (ICU), with VAP accounting for 90% of these cases [2]. HAP/VAP can be characterized as early- or late-onset relative to time of hospital admission. Early-onset HAP/VAP occur within the first 4 days of hospitalization and are not necessarily associated with antibiotic-resistant bacteria. Late-onset HAP/VAP, occurring 5 days or more after

History Received 5 February 2015 Accepted 31 March 2015 Published online 9 May 2015

hospitalization, are more likely to be caused by multidrugresistant (MDR) pathogens and are associated with increased morbidity and mortality [1]. Ceftaroline fosamil is an advanced-generation cephalosporin with broad-spectrum in vitro activity against both Gram-positive and common Gram-negative organisms. Ceftaroline has a bactericidal mechanism of action by targeting penicillin-binding proteins (PBPs), which are essential in the final steps of bacterial cell wall biosynthesis [3,4]. The spectrum of activity of ceftaroline extends to common pathogens associated with HAP/VAP, including methicillinsusceptible Staphylococcus aureus (MSSA), methicillinresistant S. aureus (MRSA), and antibiotic-susceptible enteric Gram-negative bacilli (Escherichia coli, Klebsiella pneumoniae, Enterobacter species, Proteus species and Serratia marcescens) [3,5]. Ceftaroline has a high affinity for modified PBPs, such as PBP2a in MRSA, and is therefore active

Correspondence: Keith S. Kaye, MD MPH, Professor, Medical Center and Wayne State University, University Health Center, 4201 Saint Antoine, Suite 2B, Box 331, Detroit, MI 48201, USA. Tel: +1 313-745-4439, +1 313-348-2541. Fax: +1 313-966-9898. E-mail: [email protected]  2015 Informa UK Ltd.

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DOI: 10.1080/21548331.2015.1037228

against these otherwise b-lactam-resistant strains of bacteria [3-5]. Ceftaroline is inactive against extendedspectrum b-lactamase-producing or AmpC-overexpressing Enterobacteriaceae and has limited activity against Pseudomonas aeruginosa and Acinetobacter species [3]. Ceftaroline fosamil is well tolerated with a safety profile reflective of the cephalosporin class. Ceftaroline fosamil has been approved by the US FDA for the treatment of acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia [6-9]. Ceftaroline fosamil is not indicated for the treatment of HAP/ VAP; however, it has been used off-label for this purpose [10,11]. The Clinical Assessment Program and Teflaro Utilization Registry (CAPTURE) is a retrospective cohort study designed to collect information on the contemporary clinical use of ceftaroline fosamil in the USA. The study experience for the off-label use of ceftaroline fosamil in treatment of HAP/VAP between September 2013 and March 2014 is presented.

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VAP, the location of care was the ICU. General hospital ward patients were defined as hospitalized patients who had received no care in the ICU, and the ICU patients were defined as hospitalized patients who had received any care in the ICU. Analysis populations and clinical response Patients who met all the inclusion criteria and no exclusion criteria were included in the study and comprised the enrolled population. Evaluable population comprised of all enrolled patients for whom a clinical response (success or failure) could be determined by the investigator at the time of discontinuation of ceftaroline fosamil. Clinical response was defined as success if the reason for discontinuation of ceftaroline fosamil therapy was either clinical cure with no further need for antibiotic treatment, or clinical improvement with a switch to another antibiotic. Clinical response was categorized as failure if treatment was discontinued due to either an adverse event or insufficient therapeutic effect, with the patient switched to another antibiotic.

Methods Study design and data collection

Data analysis

CAPTURE is a multicenter, registry study of adult patients treated with intravenous (IV) ceftaroline fosamil. Data were collected at participating centers in the USA for male and female patients who had been treated with ceftaroline fosamil, by random ordering and sequential review of patient charts identified from pharmacy listings. The study was approved by each institution’s ethics committee or institutional review board. We report the data collected on patient demographics, disease characteristics, isolated pathogens, the use of ceftaroline fosamil and other antibiotics, the location of care, and the clinical response for a subset of patients with a diagnosis of HAP/VAP from 16 participating centers. The analysis includes data collected between September 2013 and March 2014.

Descriptive statistics were used for all analyses. For categorical variables, descriptive statistics were frequencies (n) and percentages (%). For continuous variables, descriptive statistic included the mean, standard deviation, median and range. Statistical analyses were performed using SAS Software Version 9.2. (SAS Institute Inc. Cary, NC, USA).

Results Patient populations The total number of enrolled patients with HAP/VAP was 41, of which 40 were evaluable. Of the evaluable patients, 27 (68%) had HAP and 13 (33%) had VAP. The focus of the data presented is the evaluable population.

Patients and location of care

Patient demographics, medical history and location of care

Patients eligible for inclusion into the study were aged ‡ 18 years at the start of treatment with ceftaroline fosamil. All patients had a diagnosis of HAP/VAP, as defined by pneumonia which develops > 48 h after hospital admission, with clinical signs and symptoms consistent with a lower respiratory tract infection and chest radiography consistent with bacterial pneumonia. Patients were prescribed ceftaroline fosamil at the discretion of the treating physician; patients were non-consecutive and non-randomly selected. Patients received ‡ 4 consecutive doses of ceftaroline fosamil and the final dose was administered ‡ 30 days before the start of data collection. Patients were excluded from the study if they had received previous treatment with ceftaroline fosamil and had their information previously extracted for the study. Location of care during treatment with ceftaroline fosamil was either the general hospital ward or ICU for HAP; for

The majority of the patients with HAP/VAP receiving ceftaroline fosamil were male (58%) and the mean age at baseline was 61.3 years (Table 1). Among general hospital ward patients with HAP the mean age was 66.5 years (there were no patients with VAP who were treated in general hospital wards) and among ICU patients, the mean age was 59.7 years for patients with HAP and 57.8 years for patients with VAP. Most (n = 39, 98%) patients with HAP/VAP had relevant medical histories, 26 (96%) patients with HAP and 13 (100%) patients with VAP. Most frequent relevant medical histories were smoking, followed by structural lung disease (Table 1). Prior pneumonia, gastroesophageal reflux and congestive heart failure were other common underlying co-morbidities. The majority of patients were treated in an ICU: 14/ 27 (52%) of patients with HAP and 13/13, (100%) of patients

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Table 1. Patient demographics and comorbidities for evaluable HAP and VAP patients.

Age at baseline (years) Mean (SD) Median (range) Age group (years), n (%) < 65 ‡ 65 Gender, n (%) Male Medical historya, n (%) Smoking Structural lung disease Gastroesophageal reflux Prior pneumonia Congestive heart failure

HAP/VAP (N = 40)

HAP (N = 27)

VAP (N = 13)

61.3 (16.8) 58.5 (18–91)

63.0 (15.0) 62.0 (29–88)

57.8 (20.4) 52.0 (18–91)

24 (60.0) 16 (40.0)

15 (55.6) 12 (44.4)

9 (69.2) 4 (30.8)

23 (57.5)

16 (59.3)

7 (53.8)

21 (52.5) 19 (47.5) 10 (25.0) 10 (25.0) 8 (20.0)

15 (55.6) 16 (59.3) 7 (25.9) 8 (29.6) 6 (22.2)

6 3 3 2 2

Pathogens isolated

(46.2) (23.1) (23.1) (15.4) (15.4)

Only categories with > 20% patients are shown, other comorbidities were hemodialysis, alcoholism and stroke. Abbreviations: HAP = Hospital-acquired pneumonia; SD = Standard deviation; VAP = Ventilator-associated pneumonia. a

with VAP. Thirteen (48%) patients with HAP were treated in general hospital wards. Diagnosis and disease characteristics Among the patients with HAP/VAP, the mean duration of diagnosis prior to treatment with ceftaroline fosamil was 4.1 (± 8.2) days: 3 (± 2.5) days for HAP and 6.2 (± 14.0) days for VAP. On the day of diagnosis, similar proportions of patients with HAP and VAP (85% in both) presented with two or more clinical signs and symptoms. Abnormal auscultatory findings (85%) and dyspnea (78%) were the most common signs and symptoms among patients with HAP, and abnormal auscultatory findings (77%) and sputum production (62%) among patients with VAP. At the end of treatment with ceftaroline fosamil there was a marked decrease from baseline in the frequency of all signs and symptoms among

Approximately half of the patients with HAP (14/27; 52%) had a pathogen isolated, most commonly MRSA (12/27; 44%). Among patients with VAP, 12/13 patients (92%) had a pathogen isolated, most commonly MRSA (7/13; 54%). E. coli was isolated from 8% of patients with HAP. Other pathogens isolated from patients with VAP were P. aeruginosa (15%), Klebsiella oxytoca (15%), MSSA (8%) and E. coli (8%). Antibiotic treatment The mean duration of ceftaroline fosamil therapy was 6.9 (± 3.6) days for patients with HAP and was 7.7 (± 3.2) days for patients with VAP. Twenty-four patients (89%) with HAP received other antibiotics prior to treatment with ceftaroline fosamil, mostly vancomycin and piperacillintazobactam (74% and 44%, respectively). Prior antibiotics were administered to 10 patients (77%) with VAP, most commonly vancomycin (62%), piperacillin-tazobactam (31%) and cefepime (31%). Ceftaroline fosamil was administered as concurrent therapy in 11 patients (41%) with HAP, and 7 patients (54%) with VAP. The two patients with VAP from whom P. aeruginosa was isolated received ceftaroline fosamil as a concurrent therapy. Clinical success The overall clinical success rate for all patients with HAP/ VAP was 75% (Table 2). For patients with HAP, the overall

100 80 % of patients

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patients with HAP and most signs and symptoms among patients with VAP (Figure 1). Ten patients (25%) with HAP/VAP, all treated in the ICU, had associated bacteremia: 7/27 patients (26%) with HAP and 3/13 patients (23%) with VAP.

60 40 20 7 1 21 12 23 14 15 9 12 10 0 Pleuritic chest Dyspnea Abnormal Cough Sputum pain auscultatory production findings

2

1

6

4

10

4

4

4

8

5

Pleuritic chest Dyspnea Abnormal Cough Sputum pain auscultatory production findings

HAP (n = 27)

VAP (n = 27) Day of diagnosis

End of treatment

Figure 1. Change in frequency of each clinical sign and symptom between day of diagnosis and end of treatment for evaluable HAP and VAP patients by location of carea. a

These categories are not mutually exclusive and some patients may have had more than one sign or symptom. Abbreviations: HAP = Hospital-acquired pneumonia; VAP = Ventilator-associated pneumonia.

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Table 2. Clinical success by location of care, comorbidities, pathogens isolated and antibiotic usage.

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Patient groups Overall Patients treated in general hospital wards Patients treated in ICU Clinical success by comorbiditiesa Any medical history Smoking Structural lung disease Prior pneumonia Gastroesophageal reflux Congestive heart failure Clinical success by pathogens isolated Any pathogen isolated MRSA isolated No pathogen isolated Clinical success by antibiotic usage Ceftaroline fosamil as first-line therapy Ceftaroline fosamil as second-line therapy Ceftaroline fosamil monotherapy Ceftaroline fosamil concurrent therapy

HAP/VAP % (n/N)

HAP % (n/N)

VAP % (n/N)

75.0 (30/40) 100 (13/13) 63.0 (17/27)

81.5 (22/27) 100 (13/13) 64.3 (9/14)

61.5 (8/13) 0 61.5 (8/13)

74.4 (29/39) 71.4 (15/21) 78.9 (15/19) 80.0 (8/10) 70.0 (7/10) 87.5 (7/8)

80.8 (21/26) 80.0 (12/15) 87.5 (14/16) 87.5 (7/8) 71.4 (5/7) 100 (6/6)

61.5 50.0 33.3 50.0 66.7 50.0

61.5 (16/26) 57.9 (11/19) 100 (14/14)

64.3 (9/14) 58.3 (7/12) 100 (13/13)

58.3 (7/12) 57.1 (4/7) 100 (1/1)

50.0 (3/6) 79.4 (27/34) 81.8 (18/22) 66.7 (12/18)

100 (3/3) 79.2 (19/24) 87.5 (14/16) 72.7 (8/11)

0 (0/3) 80.0 (8/10) 66.7 (4/6) 57.1 (4/7)

(8/13) (3/6) (1/3) (1/2) (2/3) (1/2)

Only categories with > 20% patients are shown; other comorbidities were hemodialysis, alcoholism and stroke. Abbreviations: ICU = Intensive care unit; MRSA = Methicillin-resistant Staphylococcus aureus; MSSA = Methicillin-susceptible S. aureus; HAP = Hospital-acquired pneumonia; VAP = Ventilator-associated pneumonia.

a

clinical success rate for all patients was 81% and it was 62% for patients with VAP. All patients (100%) with HAP treated in general hospital wards had clinical success whereas the rate of clinical success for HAP and VAP patients treated in the ICU, as expected, was lower (Table 2). The overall clinical success rate among patients with HAP/VAP who had comorbidities was 74%: 81% for HAP and 62% for VAP. Clinical success rates for patients with baseline pathogens recovered (including MRSA) were similar for HAP and VAP (57%–64%) (Table 2). All three patients (100%) with HAP receiving ceftaroline fosamil as first-line therapy had clinical success, whereas none of the three patients with VAP receiving ceftaroline fosamil had clinical success. Among patients receiving ceftaroline fosamil as a second-line therapy, the clinical success rate was 79% for HAP and 80% for VAP. Rates of clinical success were high in patients with HAP regardless of whether ceftaroline fosamil was administered as monotherapy or concurrent therapy with another antimicrobial (88% and 73%, respectively). Among patients with VAP receiving ceftaroline fosamil as monotherapy or concurrent therapy, rates of clinical success were 67% and 57%, respectively. Treatment discontinuation, discharge destinations and readmissions Treatment with ceftaroline fosamil was discontinued due to an adverse event in one patient with HAP (3%). The nature of the adverse event was not recorded. Most of the patients with HAP were discharged to home (41%), the remaining patients were discharged to a nursing home (19%), skilled nursing facility (11%), rehabilitation facility (15%) or hospital (4%). Among patients with VAP, most were discharged to a skilled nursing facility (31%), the remaining patients were discharged to home (23%), a hospital (15%), a nursing home (8%) and a rehabilitation facility (8%). Five patients, three

(11%) with HAP and two (15%) with VAP, died. The cause of death was not recorded. In total, nine patients (seven with HAP and two with VAP) were readmitted to the same hospital within 30 days of discharge. Two patients (29%) with HAP were readmitted due to bacterial pneumonia. The reason for readmission is not known for the remaining patients with HAP and VAP.

Discussion The CAPTURE data demonstrated that treatment with ceftaroline fosamil achieved an overall clinical success rate of 75% among patients with HAP/VAP. The rates of clinical success reported in CAPTURE are similar to those reported for vancomycin (75%) and telavancin (86%) in the treatment of HAP when S. aureus was the sole pathogen; and to those reported for levofloxacin (59%) and imipenem-cilastatin (63%) in treatment of VAP [12,13]. As expected, the overall clinical success was higher among patients with HAP (82%) than among patients with VAP (62%), likely due to the difference in severity of disease between HAP and VAP. Furthermore, patients with VAP are also at higher risk of infection with MDR pathogens such as P. aeruginosa, against which ceftaroline has limited activity. Ceftaroline fosamil is therefore not recommended as empiric monotherapy for VAP. The difference in clinical success rates between patients with HAP and VAP reported in this study are similar to those reported in a Phase III study comparing ceftobiprole (77.8% for HAP and 37.7% for VAP) and linezolid (76.2% for HAP and 55.9% for VAP) for the treatment of HAP and VAP [14]. The clinical success rate for ICU patients with HAP/VAP was lower than that for patients treated in general hospital wards (63% vs. 100%), likely due to patients treated in ICU having more severe disease than those treated in general hospital wards. The CAPTURE study did not collect data on disease severity in patients at the time

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of admission; however, the increased frequency of associated bacteremia for patients in ICU is indicative of a higher level of disease severity compared with those treated in general hospital wards (37% vs. 0%). HAP/VAP, specifically late-onset HAP/VAP, is increasingly caused by antibiotic-resistant pathogens such as MRSA [1,15,16]. In the CAPTURE study, MRSA was isolated more frequently (HAP/VAP: 19/40 (48%); HAP: 12/27 (44%); and VAP: 7/13 (54%)) than any other pathogen. Ceftaroline fosamil tends to be used off-label at the discretion of the treating physician when S. aureus is isolated, and this is reflected in the high frequency of MRSA isolates in this study. It is not possible to determine whether ceftaroline was chosen based on the susceptibility of the pathogens, as CAPTURE has limited collection of MIC data and the analysis has not been performed. Further indication of this selection bias is that vancomycin, the recommended empiric therapy for suspected MRSA infection, was the most common antibiotic prescribed prior to ceftaroline fosamil [1]. Ceftaroline fosamil had a clinical success rate of 58% among HAP/VAP patients with MRSA infection, similar to that reported for tigecycline (40%) in a Phase III clinical trial for the treatment of HAP/ VAP due to MRSA and that reported for vancomycin (69%) in a retrospective, multicenter study of ICU patients with MRSA VAP [17,18]. However, caution should be exercised when comparing the results from a retrospective study such as CAPTURE with those of randomized clinical trials. The CAPTURE data reflect the use of ceftaroline fosamil in realworld clinical situations, unlike the controlled conditions of a clinical study. The majority of patients with HAP/VAP (85%) in the CAPTURE study received ceftaroline fosamil as second-line therapy after failure of prior antibiotics, most commonly vancomycin (74% of patients with HAP and 62% of patients with VAP) and piperacillin/tazobactam (44% of patients with HAP and 31% of patients with VAP). The CAPTURE study did not collect data on reasons for previous antibiotic failure during the time frame covered by this manuscript (i.e. September 2013 – March 2014). Ceftaroline fosamil showed a high clinical success rate among patients with HAP (79%) and patients with VAP (80%) who received it as second-line therapy. Treatment failure in the three patients with VAP who received ceftaroline fosamil as first-line therapy was likely due to the presence of Gram-negative pathogens against which ceftaroline has no or limited activity. One patient had P. aeruginosa and Morganella morganii; another patient, P. aeruginosa and K. oxytoca; and the third, K. oxytoca and MRSA (susceptible to both ceftaroline and vancomycin). Patients who received ceftaroline fosamil monotherapy had a higher clinical success rate (88% of patients with HAP and 67% of patients with VAP) than those who received concurrent therapy (73% and 57%, respectively). This may be indicative of selective prescribing of concurrent therapy to those patients with more severe illness or suspected or confirmed polymicrobial infection. Registry studies are limited due to the retrospective study design, the lack of a comparator group, patient selection bias, and the lack of randomization of treatment allocation. Specifically, CAPTURE is a non-blinded descriptive study; its

Hosp Pract, 2015; 43(3):144–149

subjective descriptions of clinical findings are the only outcomes data collected, and without a comparator arm in the study, there is limited comment that can be made on clinical outcome when comparing ceftaroline fosamil with other agents. Nevertheless, registry studies such as CAPTURE have the potential to provide valuable information on the contemporary, including off-label, use of antibiotics, such as the spectrum of usage, duration and effectiveness of treatment, and can be used to generate hypotheses for further clinical investigation. The results from this study demonstrate favorable clinical success rates for the use of ceftaroline fosamil in the treatment of HAP and VAP, both in general hospital wards and the ICU. Ceftaroline fosamil was an effective treatment option for patients, despite the wide range of co-morbidities, high levels of disease severity and ventilator-dependence, and the inclusion of patients who had received prior unsuccessful antibiotic therapy.

Conclusion The CAPTURE study data support further evaluation of ceftaroline fosamil as an effective treatment option for HAP and VAP as monotherapy when a ceftaroline-susceptible etiologic pathogen is identified; or, in some instances, as concurrent therapy with another agent when resistant Gram-negative pathogens are suspected.

Acknowledgements We thank the participating sites, investigators and their staff for their contribution to this study.

Declaration of interest Writing and editorial services for this manuscript were provided by Micron Research Limited and funded by Actavis plc. KS Kaye and G Udeani are study investigators for CAPTURE, the ceftaroline fosamil study funded by Cerexa, Inc., a wholly owned subsidiary of Forest Laboratories. KS Kaye and G Udeani are also consultants for Cerexa, Inc., a wholly owned subsidiary of Forest Laboratories. Actavis acquired Forest Laboratories in July 2014. P Cole and HD Friedland are former employees of Cerexa, Inc., a wholly owned subsidiary of Forest Laboratories, and have received stock and stock options from Forest Laboratories. Actavis acquired Forest Laboratories in July 2014. As a result of the acquisition, P Cole and HD Friedland are shareholders of Actavis plc. HD Friedland is also a consultant for Actavis plc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

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[10] Arshad S, Hartman P, Zervos MJ. A novel treatment option for MRSA pneumonia: ceftaroline fosamil-yielding new hope in the fight against a persistent infection. Expert Rev Anti Infect Ther 2014;12:727–9. [11] Pasquale TR, Tan MJ, Trienski TL, File TM Jr. Methicillin-resistant Staphylococcus aureus nosocomial pneumonia patients treated with ceftaroline: retrospective case series of 10 patients. J Chemother 2015;27:29–34. [12] Corey GR, Kollef MH, Shorr AF, Rubinstein E, Stryjewski ME, Hopkins A, Barriere SL. Telavancin for hospital-acquired pneumonia: clinical response and 28-day survival. Antimicrob Agents Chemother 2014;58:2030–7. [13] Shorr AF, Zadeikis N, Jackson WL, Ramage AS, Wu SC, Tennenberg AM, Kollef MH. Levofloxacin for treatment of ventilator-associated pneumonia: a subgroup analysis from a randomized trial. Clin Infect Dis 2005;40:S123–9. [14] Awad SS, Rodriguez AH, Chuang YC, Marjanek Z, Pareigis AJ, Reis G, et al. A phase 3 randomized double-blind comparison of ceftobiprole medocaril versus ceftazidime plus linezolid for the treatment of hospital-acquired pneumonia. Clin Infect Dis 2014;59:51–61. [15] Gupta A, Agrawal A, Mehrotra S, Singh A, Malik S, Khanna A. Incidence, risk stratification, antibiogram of pathogens isolated and clinical outcome of ventilator associated pneumonia. Indian J Crit Care Med 2011;15:96–101. [16] Wisplinghoff H, Bischoff T, Tallent SM, Seifert H, Wenzel RP, Edmond MB. Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis 2004;39:309–17. [17] Freire AT, Melnyk V, Kim MJ, Datsenko O, Dzyublik O, Glumcher F, et al. Comparison of tigecycline with imipenem/cilastatin for the treatment of hospital-acquired pneumonia. Diagn Microbiol Infect Dis 2010;68:140–51. [18] Peyrani P, Wiemken TL, Kelley R, Zervos MJ, Kett DH, File TM Jr, et al. Higher clinical success in patients with ventilatorassociated pneumonia due to methicillin-resistant Staphylococcus aureus treated with linezolid compared with vancomycin: results from the IMPACT-HAP study. Crit Care 2014;18:R118.

Ceftaroline fosamil for the treatment of hospital-acquired pneumonia and ventilator-associated pneumonia.

Ceftaroline fosamil is a novel cephalosporin with bactericidal activity against common pathogens associated with hospital-acquired pneumonia (HAP) and...
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